.alpha.-substituted boronic esters such as .alpha.-halo boronic esters are highly promising and useful intermediates in a variety of organic syntheses. They are especially valuable in the synthesis of .alpha.-amino boronic esters, as described in Tetrahedron Lett., 1992, 33, 4209-4212, S. Elgendy, J. Deadman, G. Patel, D. Green, N. Chino, C. Goodwin, M. F. Scully, V. V. Kakkar and G. Claeson. These compounds are also useful in the synthesis of peptides, for example as described in published International Patent Application No. WO 92/07869.
A review of uses of .alpha.-halo boronic esters is given in Chem. Rev., 1989, 89, 1535-1551, D. S. Matteson.
Hitherto in the literature only two methods have been reported for the direct synthesis of .alpha.-halo boronic esters via hydroboration, as described in J. Am. Chem. Soc., 1968, 90, 2915, H. C. Brown and R. L. Sharp.
Firstly, as disclosed in U.S. Pat. No. 3,093,674 (W. H. Schechter), (MeO).sub.2 BCHClCH.sub.2 Cl has been synthesized by the reaction of (MeO).sub.2 BH with E-1,2-dichloroethane. The product obtained from the hydrolysis however was contaminated with boric acid, which is corrosive and difficult to remove and therefore reduces the usefulness of the prepared ester in subsequent applications, particularly in peptide synthesis.
Secondly, as disclosed in J. Am. Chem. Soc., 1968, 90 6259-6260, D. J. Pasto, J. Hickman, T-C. Cheng, an alternative method which has been used to prepare .alpha.-halo boronic acids is the hydroboration of 1-chloro-2-methyl propene with an equivalent of borane followed by hydrolysis, which yielded (1-chloro-2-methyl propyl) boronic acid. However, if the hydroboration mixture was allowed to stand in THF at room temperature for several hours or if excess BH.sub.3, were added, the intermediate .alpha.-substituted borane rearranged to isobutyl chloro borane. These reactions are illustrated by the following reaction scheme: ##STR3## In EP-A-0212708 there are described special catalysts containing rhodium or ruthenium which are useful in the hydroboration (by catecholborane) of various unsaturated hydrocarbon species such as alkenes and alkynes. However, this disclosure is limited to the hydroboration of unsaturated compounds which are unsubstitued.